The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index; 10 of the 34 sources its claims cite were checked for support.
Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons
Open accessAbstract
Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.
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TL;DR
Using two-photon uncaging of a newly developed caged glutamate, this study mapped functional AMPA receptors on individual dendritic spines of hippocampal CA1 pyramidal neurons. It finds that AMPA receptor expression is tightly correlated with spine-head geometry, with mushroom spines bearing many receptors and thin spines/filopodia few, suggesting independent regulation at single spines.
Key findings
- AMPA-type glutamate receptors are abundant in mushroom spines (up to 150/spine) but sparsely distributed in thin spines and filopodia; thin spines and filopodia may serve as structural substrates of silent synapses.
- Glutamate sensitivity of individual spines correlated strongly with spine-head volume: correlation coefficient r = 0.69–0.90 (0.80 ± 0.07; n = 9) within one dendrite, 0.89 in one example, and 0.77 for the average of 9 dendrites; correlation with spine length was weak and negative (r = 0.30).
- Nonstationary fluctuation analysis estimated 46–147 AMPA receptors in mushroom spines (82 ± 31; mean ± s.d., n = 8), with single-channel currents of 0.4–0.8 pA (0.6 ± 0.1 pA); estimated opening probability was 0.27, suggesting postsynaptic AMPA receptors are not saturated by glutamate from a single vesicle.
- Autocorrelation analysis along dendrites showed no correlation even in neighboring spines for glutamate sensitivities or spine-head volumes, suggesting AMPA receptor expression is controlled independently at the level of individual spines.
Methods
- Two-photon uncaging of MNI-glutamate combined with whole-cell patch-clamp electrophysiology and fluorescence imaging in cultured hippocampal neurons and acute hippocampal slices from rats (cultured neurons from P1 Wistar rats, used at 17–25 days; slices from 15–22 day old Sprague–Dawley rats unless otherwise stated; some young animals 7–9 days old).
- Functional mapping used pseudorandom scanning at 0.33 μm lateral intervals and z-axis sections separated by 0.8 μm, recording 2pEPSCs at −70 mV; spine-head volume was estimated from fluorescence images, and autocorrelation and nonstationary fluctuation analysis (with 0.1 mM cyclothiazide) were used.
- Analysis included kinetic/diffusion modeling of glutamate concentration and AMPA receptor opening, correlation coefficients, coefficients of variation, and estimation of receptor number and single-channel current.
Limitations
- Stated in the paper: the mechanism by which spine-head volume affects AMPA receptor trafficking remains to be determined, and whether thin spines, filopodia, and dendritic shafts transform into thicker spines after long-term potentiation is unknown. Spatial resolution in slices was slightly reduced (0.6 μm laterally and 1.4 μm axially) because of the lower numerical aperture lens, so dendrites with relatively sparse spines (~1 spine/μm) were studied; correlation values were reduced by channel noise (CV ~0.08) and sampling error (CV = 0.1).
- Evident from the text: experiments were performed at room temperature (23–25°C), in cultured neurons or acute slices from juvenile rats, and the main structure–function relationship is correlational rather than causal; some analyses relied on small samples (e.g., n = 7–9 dendrites, n = 8 for fluctuation analysis).
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10 of 34 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Nevertheless, two-photon excitation of MNI-glutamate permits the functional mapping of glutamate sensitivity with a spatiotemporal resolution similar to that achieved by activation of presynaptic terminals (~0.4μm and ~0.1 ms)28.”
What the sources say
- Could not verifycites [28] Rusakov, D. A. & Kullmann, D. M. Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural constraints, uptake, and receptor activation. J. Neurosci. 18, 3158–3170 (1998). sourceExperimental — accuracy not yet measured
The Synaptic currents and Activation of extrasynaptic receptors sections discuss modeled glutamate diffusion and receptor activation at distances around 400–465 nm; they do not describe the resolution of functional mapping. Searches for MNI-glutamate, two-photon excitation, and the claimed 0.1 ms resolution found no passage addressing the comparison with presynaptic-terminal activation. Page numbers were not available in our copy. (LLM, conf=0.76)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This observation suggests that the expression of AMPA receptors is controlled independently at a level of the individual spine, consistent with the classical notion that a single spine may behave as an independent chemical compartment to regulate synaptic transmission13, 14.”
What the sources say
- Partly supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). sourceExperimental — accuracy not yet measured
The Serial electron microscopy section (p. 2983) proposes that constricted spine necks might limit diffusion to neighboring synapses, supporting the cited notion of a spine as a possible chemical compartment. The discussion of spine geometry and synaptic efficacy (page not specified in our copy) likewise treats compartmentation as a possibility. Neither passage establishes that AMPA-receptor expression is controlled independently at each spine. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [14] Yuste, R. & Denk, W. Dendritic spines as basic functional units of neuronal integration. Nature 375, 682–684 (1995). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition, our study suggests that thin spines and filopodia may be postsynaptic components of silent synapses28, 32, 34, 44.”
What the sources say
- Could not verifycites [28] Rusakov, D. A. & Kullmann, D. M. Extrasynaptic glutamate diffusion in the hippocampus: ultrastructural constraints, uptake, and receptor activation. J. Neurosci. 18, 3158–3170 (1998). sourceExperimental — accuracy not yet measured
The Activation of extrasynaptic receptors section discusses NMDA-receptor activation at neighboring synapses and notes that dendritic spines may change shape, but does not identify thin spines or filopodia as components of silent synapses. Searches for “filopodia,” “thin spines,” and “silent synapses” found no passage making that connection; silent synapses appear in the References. (LLM, conf=0.74)
- Not checked — no full text of the sourcecites [32] Gomperts, S. N., Rao, A., Craig, A. M., Malenka, R. C. & Nicoll, R. A. Postsynaptically silent synapses in single neuron cultures. Neuron 21, 1443–1451 (1998). source
- Not checked — no full text of the sourcecites [34] Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71–75 (1996). source
- Partly supportedcites [44] Fiala, J. C., Feinberg, M., Popov, V. & Harris, K. M. Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J. Neurosci. 18, 8900–8911 (1998). sourceExperimental — accuracy not yet measured
The Results report synapses on filopodia, and the Analysis describes how the postsynaptic process was identified as a spine or filopodium. The paper also mentions thin spines, but our copy does not identify synapses on either structure as silent; that qualification is unsupported. (LLM, conf=0.82)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Regions of glutamate sensitivity tended to be asymmetrically localized to one portion of a spine (Figs. 3h and 4c–j), consistent with the predominant localization of AMPA receptors within PSDs with a diameter of 0.1 to 0.5μm13, 19, 20.”
What the sources say
- Partly supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). sourceExperimental — accuracy not yet measured
The citation follows the sentence’s PSD explanation, while the asymmetric glutamate-sensitivity observation is presented as the citing paper’s own finding. In “Relationships between hippocampal spine geometry and,” Harris and Stevens describe PSDs as occupying only a small portion of spine surface and suggest that larger PSDs contain more receptors. Our copy does not establish that the receptors are specifically AMPA receptors or give the stated 0.1–0.5 μm PSD diameter. (LLM, conf=0.79)
- Partly supportedcites [19] Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545–559 (1998). sourceExperimental — accuracy not yet measured
The paper’s Figure 9 caption shows AMPA-receptor labeling at synaptic junctions on spines, supporting the localization invoked to explain the citing authors’ own glutamate-sensitivity observations. It also shows labeling in the spine apparatus and extrasynaptic membrane, and the passages do not establish the stated PSD diameter of 0.1–0.5 μm. The asymmetric glutamate-sensitivity finding is attributed to the citing paper’s figures, not to this source. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [20] Takumi, Y., Ramirez-Leon, V., Laake, P., Rinvik, E. & Ottersen, O.P. Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat. Neurosci. 2, 618–624 (1999). source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The relationship between spine geometry and expression of functional AMPA receptors demonstrated here provides substantial support to the hypothesis that neuronal fine structures have functional correlates in the brain13, 18, 21.”
What the sources say
- Supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). source
In “Serial electron microscopy,” the paper reports that spine-head dimensions correlate with postsynaptic density area and presynaptic vesicle number, and interprets this as evidence that spine-head dimensions reflect synaptic efficacy. That supports the cited hypothesis that neuronal fine structure has functional correlates. The AMPA-receptor relationship is described as demonstrated in the citing paper itself, not attributed to this source; page numbers are not shown for the decisive passages. (LLM, conf=0.90)
- Not matchedcites [18] Cajal, R. y. Histologie du Systeme Nerveux de l'Homme et des Vertebres (Maloine, Paris, 1911).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [21] Segal, M., Korkotian, E. & Murphy, D. D. Dendritic spine formation and pruning: common cellular mechanisms? Trends Neurosci. 23, 53–57 (2000). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Under physiological conditions, MNI-glutamate was stable for 24 hours, and did not activate any current at a concentration of 10 mM.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“This uncaging regime produced little or no photodamage29, as shown by the stability of the amplitudes of the 2pEPSCs over 1 min (Fig. 1h).”
What the sources say
- Not checked — no full text of the sourcecites [29] Hopt, A. & Neher, E. Highly nonlinear photodamage in two-photon fluorescence microscopy. Biophys. J. 80, 2029–2036 (2001). source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Under physiological conditions, MNI-glutamate was stable for 24 hours, and did not activate any current at a concentration of 10 mM.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The time course of 2pEPSC is well-predicted (smooth line in Fig. 1c) from rapid photolysis (10μs) of MNI-glutamate within a focal volume of two-photon excitation with lateral and axial full-width-at-half-maximal (FWHM) diameter of 0.29 and 0.89μm, respectively (black lines in Fig. f and g; see Methods).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The spatial resolution of glutamate receptor activation was inferred from a small, isolated, glutamate-sensitive region of a dendrite (Fig. 2d), yielding lateral and axial FWHM diameters of 0.45 and 1.1μm, respectively (green lines in Fig. 1f and g).”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 13
- Probably not a substantial claim. 16
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Given that each spine receives only one synaptic input13, our data indicate the highest possible degree of freedom is available in synaptic connections in the dendrites, which has been assumed in the learning models of most neural network theories17.”
What the sources say
- Partly supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [17] Arbib, M. A. The Handbook of Brain Theory and Neural Networks (MIT Press, Cambridge, Massachusetts, 1995). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“These data are consistent with the correlation between AMPA receptor immunoreactivity and the size of PSD19, 20, because the size of PSD is nearly proportional to the spine-head volume13.”
What the sources say
- Supportedcites [19] Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545–559 (1998). source
Figure 4B and 4D report significant positive correlations between synapse size and AMPA-receptor immunoparticle content in Schaffer collateral and mossy fiber synapses. The separate claim about spine-head volume is attached to citation 13, not to this source. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [20] Takumi, Y., Ramirez-Leon, V., Laake, P., Rinvik, E. & Ottersen, O.P. Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat. Neurosci. 2, 618–624 (1999). source
- Supportedcites [13] Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989). source
The Serial electron microscopy section reports that PSD area is positively correlated with spine volume, much more strongly with spine-head volume than with spine-neck volume. The Discussion describes spine-head dimensions as proportional to PSD area. The AMPA receptor immunoreactivity correlation is attached to other citations, not this source. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, it did not affect either the amplitude (Fig. 1b) or the time course (Fig. 1b, inset) of miniature excitatory postsynaptic currents (mEPSCs), indicating that it does not exert an antagonistic effect at AMPA receptors.”
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We developed a methoxy derivative of nitroindolino-glutamate, MNI-glutamate (Fig. 1a), that possesses a two-photon cross section (0.06 GM; 1 GM = 10−50 cm4s/photon2) sufficiently large for biological application (see Methods).”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thin spines exhibited little (Fig. 4a and b) or slight glutamate sensitivity (Fig. 4c–e), and thick mushroom spines displayed large sensitivity to uncaged glutamate (Fig. 4f–j).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The spatial resolution of AMPA-receptor mapping was slightly reduced compared with cultured neurons, 0.6μm laterally and 1.4μm axially, because of the smaller numerical aperture (NA) of the lens used (0.9).”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In young animals (7 to 9 days old), dendrites were decorated only sparsely with spines34, and most of the dendritic shaft was devoid of glutamate sensitivity (Fig. 4l), although marked expression of functional AMPA receptors was already apparent in mushroom spines present (Fig. 4l).”
What the sources say
- Not checked — no full text of the sourcecites [34] Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71–75 (1996). source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The glutamate sensitivity of each PSD (as defined by the maximum glutamate sensitivity of a spine) was significantly correlated with the volume of the spine head (Fig. 5a); the correlation coefficient (r) was 0.69–0.90 (0.80 ± 0.07; n = 9) within one dendrite (0.89, Fig. 5b) and 0.77 for average of 9 dendrites (Fig. 5c).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The maximal glutamate sensitivity of a spine reflects the number of functional AMPA receptors in that spine.
In the paper
“The two-photon action cross section of MNI-glutamate was obtained as 0.06 GM at 730 nm, using azid-1 as a standard compound with a known action cross section of 1.0 GM at 730 nm48.”
What the sources say
- Not checked — no full text of the sourcecites [48] Brown, E. B., Shear, J. B., Adams, S. R., Tsien, R. Y. & Webb, W. W. Photolysis of caged calcium in femtoliter volumes using two-photon excitation. Biophys. J. 76, 489–499 (1999). source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The time course of 2pEPSC (Fig. 3bA–C) is similar to spontaneous mEPSCs (Fig. 3bE).”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also detected slow NMDA-mediated currents when Mg2+ was removed from the extracellular solution; the distribution of these currents was less heterogeneous than that of AMPA receptors, and most spines expressed NMDA receptors (data not shown).”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For instance, the peak glutamate concentration at the center of irradiation reaches 0.6 mM focally, at a laser power of 7 mW, MNI-glutamate concentration (CMNI) of 8 mM, the duration of irradiation (td) of 50 μs.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and those larger than 20 μs predict greater loss of spatial resolution than actually obtained (Fig. 1f)”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The evoked currents had a small coefficient of variation (CV) of 0.08, consistent with the post-synaptic action of glutamate23.”
What the sources say
- Not checked — no full text of the sourcecites [23] Liu, G., Choi, S. & Tsien, R. W. Variability of neurotransmitter concentration and nonsaturation of postsynaptic AMPA receptors at synapses in hippocampal cultures and slices. Neuron 22, 395–409 (1999). source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the condition listed above, the peak opening probability was 0.15 and 0.2 for 2pEPSC and mEPSC, respectively.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This might result from less effective transport of AMPA receptors into thinner spines with smaller volume-to-surface ratios.”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The animal experiments were approved by the animal experiment committee of the National Institute for Physiological Sciences, Japan.”
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In the paper
“The spine-head volume was estimated by total fluorescence of the spine head in the fluorescence images, which was calibrated using the large spine head whose volume (0.087μm3, spine A in Fig. 3f) could be directly estimated by a FWHM diameter.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The error due to the sampling intervals was estimated as 0.1 (CV), given the spatial resolution of glutamate mapping as 0.6μm laterally and 1.4μm axially.”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such a weak correlation may be due to the presence of several spines with long length and small spine-head volume (Fig. 5e).”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“These data conform with the development of AMPA receptor immunoreactivity in CA1 pyramidal neurons35.”
What the sources say
- Not checked — no full text of the sourcecites [35] Petralia, R. S. et al. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat. Neurosci. 2, 31–36 (1999). source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The point spread function of the focal volume of two-photon excitation were estimated using a 0.1μm fluorescent beads as 0.29 μm (FWHM) laterally and 0.89 μm axially for the inverted microscope (NA, 1.2), and 0.39μm laterally and 1.28μm axially for the upright microscope (NA, 0.9).”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The access resistance was 70% compensated for the experiments shown in Fig. 1c–g but not for others.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We estimated the CV of the two-photon excitation to be less than 0.03, by measuring the two-photon excited fluorescence of a polar tracer, Alexa Fluor 594 hydrizide (0.2 mM, Molecular Probes, Eugene, Oregon), applied to slice preparations similarly to MNI-glutamate.”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using two-photon excitation of a caged-glutamate compound, we showed that the expression of functional AMPA receptors among spines shows a large range (CV, 0.5), varying from the minimal (silent) to those bearing more than 140 AMPA channels, and has a strong correlation with spine-head volume.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This powerful approach thus allows the optical stimulation of dendritic processes in brain slices at the level of the individual synapse.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
The maximal glutamate sensitivity of a spine reflects the number of functional AMPA receptors in that spine.
“The glutamate sensitivity of each PSD (as defined by the maximum glutamate sensitivity of a spine) was significantly correlated with the volume of the spine head (Fig. 5a);”
The paper relies on this without support.
In the presence of 0.1 mM cyclothiazide, the opening probability of AMPA receptors is greater than 0.5.
“We added the desensitization inhibitor cyclothiazide (0.1 mM, CTZ) to increase the opening probability of AMPA receptors to greater than 0.5.”
The paper relies on this without support.
The largest mEPSC (~19 pA) likely occurred in the mushroom spines with the largest number of AMPA receptors (N = 147, i = 0.48 pA).
“because the opening probability of the AMPA receptors was estimated as 0.27, given that the largest mEPSC was ~19 pA (n = 222) in our experiments, and that such mEPSC likely occurred in the mushroom spines with largest number of AMPA receptors (N = 147, i = 0.48 pA).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Spine head size is positively correlated with mEPSC amplitude [65], and the functional loss of NMDA receptors in DG granule cells has been associated with impairments in pattern separation [8].”
From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [65]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Given that large spines have been shown to express AMPA receptors abundantly8”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [8]
In the citing paper
“Two-photon uncaging allows the release of glutamate within a small focal volume8, so that activation of glutamate receptors is limited to a region within ca. 1 μm of the uncaging beam.”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [8]
In the citing paper
“which express a small number of AMPA receptors8.”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [8]
In the citing paper
“Amplitudes of AMPA currents were 1–25 pA, (measured with perforated patch-clamp experiments), which were within the range of miniature excitatory postsynaptic currents8.”
From Structural basis of long-term potentiation in single dendritic spines (2004) · cites this paper as [8]
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“This evidence agrees with previous data in hippocampal CA1 neurons showing that spine enlargement is associated with an increase in AMPA-R-mediated currents and that it is dependent on NMDA-Rs (Matsuzaki et al., 2001).”
ResultThe Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism
Eagleson, K. L., Xie, Z., & Levitt, P. R. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.08.035 · Cited by 33
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Compatibility between itinerant synaptic receptors and stable postsynaptic structure
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Two-Photon Excitation Microscopy and Its Applications in Neuroscience
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ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function
Ba, W., Selten, M. M., van der Raadt, J., van Veen, H., Li, L., Benevento, M., Oudakker, A. R., Lasabuda, R. S. E., Letteboer, S. J. F., Roepman, R., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.037 · Cited by 42
“Due to the tight correlation between synaptic strength and spine size, the increase in synaptic strength could occur as a consequence of the changes in spine size (Matsuzaki et al., 2001; Nimchinsky et al., 2002).”
Relationship Between Synaptic AMPAR and Spine Dynamics: Impairments in the FXS Mouse
Suresh, A., & Dunaevsky, A. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx128 · Cited by 33
“Levels of synaptic AMPAR determine the strength of a synapse (Matsuzaki et al. 2001) and have been associated with synaptic stability (Grutzendler et al. 2002; Trachtenberg et al. 2002; Holtmaat et al. 2005).”
BackgroundLetellier, M., Levet, F., Thoumine, O. R., & Goda, Y. (2019) · PLoS Biology · doi:10.1371/journal.pbio.2006223 · Cited by 32
“Furthermore, whereas the sizes of dendritic spines are readily visualized and serve as a proxy for postsynaptic strengths [8,10,34,54], axonal bouton volumes or the total synaptic vesicle pool sizes are poorly correlated to presynaptic strengths [55,56].”
BackgroundMethodMartín‐Belmonte, A., Aguado, C., Alfaro‐Ruiz, R., Itakura, M., Moreno‐Martínez, A. E., de la Ossa, L., Molnár, E., Fukazawa, Y., & Luján, R. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.577996 · Cited by 34
Rouxel, C., Charlot, M., Mongin, O., et al. (2012) · Chemistry - A European Journal · doi:10.1002/chem.201202832 · Cited by 33
Penrod, R. D., Kourrich, S., Kearney, E., Thomas, M. J., & Lanier, L. M. (2011) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2011.05.029 · Cited by 35
Kanemoto, Y., Matsuzaki, M., Morita, S., Hayama, T., Noguchi, J., Senda, N., Momotake, A., Arai, T., & Kasai, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022652 · Cited by 37
“Mapping of GABA-mediated currents was performed as described previously for glutamate uncaging [1].”
InfluentialSelf-citationJakkampudi, S., Abe, M., Komori, N., et al. (2016) · ACS Omega · doi:10.1021/acsomega.6b00119 · Cited by 33
Self-citationGeometric Control of Frequency Modulation of cAMP Oscillations due to Calcium in Dendritic Spines
Ohadi, D., & Rangamani, P. (2019) · Biophysical Journal · doi:10.1016/j.bpj.2019.10.004 · Cited by 31
Studying Signal Transduction in Single Dendritic SpinesPreprint
Yasuda, R. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005611 · Cited by 33
“In particular, because the development of MNI-glutamate, a caged glutamate with a high two-photon cross section, two-photon glutamate uncaging has been applied to study the physiology of single dendritic spines (Matsuzaki et al. 2001).”
BackgroundSerita, T., Fukushima, H., & Kida, S. (2017) · Scientific Reports · doi:10.1038/srep42528 · Cited by 37
“By contrast, mushroom spines have larger PSDs 47 , which anchor more AMPA glutamate receptors and make these synapses functionally stronger 48–50 , and persist for months 51 .”
Stojakovic, A., Chang, S.-Y., Nesbitt, J. J., Pichurin, N. P., Ostroot, M., Aikawa, T., Kanekiyo, T., & Trushina, E. V. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-201015 · Cited by 31
“LTP in the CA1 region represents a form of plasticity responsible for learning and memory, and it critically relies on the activation of NMDARs for its induction and increased insertion of AMPARs for its expression [60].”
BackgroundInfluentialStructural plasticity of spines at giant mossy fiber synapses
Zhao, S., Studer, D., Chai, X., Graber, W. A., Brose, N., Nestel, S., Young, C. C., Rodriguez, E., Saetzler, K., & Frotscher, M. (2012) · Frontiers in Neural Circuits · doi:10.3389/fncir.2012.00103 · Cited by 40
Modeling of Autism Genetic Variations in Mice: Focusing on Synaptic and Microcircuit Dysfunctions
Qiu, S., Aldinger, K. A., & Levitt, P. R. (2012) · Developmental Neuroscience · doi:10.1159/000336644 · Cited by 33
Deller, T., Orth, C. B., Vlachos, A., Merten, T., Turco, D. D., Dehn, D., Mundel, P. H., & Frotscher, M. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.21103 · Cited by 32
“…at their postsynaptic membrane, and the intracellular composition of spines determine how presynaptic neuronal activity is propagated to the postsynaptic neuron (Svoboda et al., 1996; Matsuzaki et al., 2001, 2004; Korkotian et al., 2004; for review see Hayashi and Majewska, 2005; Segal, 2005).”
BackgroundMethodInfluentialBasu, S., Plewczyński, D., Saha, S., Roszkowska, M., Magnowska, M., Bączyńska, E., & Włodarczyk, J. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw172 · Cited by 32
Luteinizing Hormone Involvement in Aging Female Cognition: Not All Is Estrogen Loss
Bhatta, S., Blair, J. A., & Casadesús, G. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00544 · Cited by 34
Iketaki, Y., Watanabe, T., Sakai, M., Ishiuchi, S., Fujii, M., & Watanabe, T. (2005) · Optical Engineering · doi:10.1117/1.1871512 · Cited by 32
High-resolution iontophoresis for single-synapse stimulation
Murnick, J. G., Dubé, G., Krupa, B., & Liu, G. (2002) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(02)00028-6 · Cited by 32
Ruediger, J., van der Zee, E. A., Strijkstra, A. M., Aschoff, A., Daan, S., & Hut, R. A. (2007) · Synapse · doi:10.1002/syn.20380 · Cited by 32
Soeller, C., Jacobs, M. D., Donaldson, P. J., et al. (2003) · Journal of Biomedical Optics · doi:10.1117/1.1582468 · Cited by 32
Self-citationVadakkan, K. I. (2015) · SpringerPlus · doi:10.1186/s40064-015-1283-1 · Cited by 31
“In addition to changes that can accompany AMPA receptor expression (Matsuzaki et al. 2001), enlargement of the dendritic spines by dopamineinduced mechanisms (Yagishita et al.”
BackgroundStaffend, N. A., & Meisel, R. L. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.09.064 · Cited by 30
“In addition to changes in spine density, we analyzed spine morphology based on observations that spine shape is strongly correlated with synaptic efficacy (Kasai et al., 2003; Matsuzaki et al., 2001).”
MethodMacGillavry, H. D., & Hoogenraad, C. C. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.02.024 · Cited by 35
“For instance, bigger spine heads contain larger PSDs and a higher number of AMPA-type glutamate receptors (AMPARs) [1,2].”
Distinct roles of NMDA receptors at different stages of granule cell development in the adult brain
Mu, Y., Zhao, C., Toni, N., Yao, J., & Gage, F. H. (2015) · eLife · doi:10.7554/elife.07871 · Cited by 31
“The size of the spine head has been positively correlated with synaptic AMPAR level (Matsuzaki et al., 2001).”
BackgroundInfluentialCooperative Veratryle and Nitroindoline Cages for Two‐Photon Uncaging in the NIR
Cueto-Diaz, E. J., Picard, S., Klausen, M., Hugues, V., Pagano, P., Génin, E., & Blanchard-Desce, M. H. (2016) · Chemistry - A European Journal · doi:10.1002/chem.201601109 · Cited by 31
Gordon‐Weeks, P. R. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.06.015 · Cited by 31
“Spine head volume correlates closely with the area of the PSD (Harris and Stevens, 1989) and the number of AMPA receptors (Matsuzaki et al., 2001).”
BackgroundSaravia, R., Flores, Á., Plaza‐Zabala, A., Busquets-García, A., Pastor, A., de la Torre, R., Marzo, V. D., Marsicano, G., Ozaita, A., Maldonado, R. J., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.07.007 · Cited by 32
“Thus, AMPA glutamate receptors including GluR2 subunits (51) modulate synaptic strength, and are abundant in mushroom spines, but sparsely distributed in thin and filopodia spines of CA1 hippocampal pyramidal neurons (52).”
Dickstein, D. L., Talty, R., Bresnahan, E. R., Varghese, M., Perry, B. C., Janssen, W. G. M., Sowa, A., Giedzinski, E., Apodaca, L. A., Baulch, J. E., et al. (2018) · The Journal of Comparative Neurology · doi:10.1002/cne.24530 · Cited by 33
Evidence for sleep-dependent synaptic renormalization in mouse pups
de Vivo, L., Nagai, H., Wispelaere, N. D., Spano, G. M., Marshall, W., Bellesi, M., Nemec, K. M., Schiereck, S. S., Nagai, M., Tononi, G., et al. (2019) · SLEEP · doi:10.1093/sleep/zsz184 · Cited by 30
Optical analysis of glutamate spread in the neuropil
Matthews, E. A., Sun, W., McMahon, S. M., Doengi, M., Halka, L., Anders, S., Müller, J. A., Steinlein, P., Vana, N., van Dyk, G., et al. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhab440 · Cited by 31
“2-Photon (2P)-based glutamate uncaging (MNI-cagedglutamate) can be used to generate a small and transient source of glutamate in brain tissue (Matsuzaki et al. 2001).”
MethodVanderplow, A. M., Kermath, B. A., Bernhardt, C. R., Gums, K. T., Seablom, E. N., Radcliff, A. B., Ewald, A. C., Jones, M. V., Baker, T. L., Watters, J. J., et al. (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001502 · Cited by 32
Reverse Engineering Caged Compounds: Design Principles for their Application in Biology
Ellis‐Davies, G. C. R. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202206083 · Cited by 33
Self-citationWu, H., Chen, X., Shen, Z., Li, H., Liang, S., Lu, Y., & Zhang, M. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.11.011 · Cited by 33
Hippocampal synaptic connectivity in phenylketonuria
Horling, K., Schlegel, G., Schulz, S., Vierk, R., Ullrich, K., Santer, R., & Rune, G. M. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu515 · Cited by 31
Amuti, S., Tang, Y., Wu, S., Liu, L., Huang, L., Zhang, H., Li, H., Jiang, F., Wang, G., Liu, X., et al. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.11.020 · Cited by 33
Chromophores for the Delivery of Bioactive Molecules with Two-Photon Excitation
Dore, T. M., & Wilson, H. C. (2011) · Neuromethods · doi:10.1007/978-1-61779-031-7_4 · Cited by 30
Activity-dependent structural plasticity of Purkinje cell spines in cerebellar vermis and hemisphere
Bartolo, P. D., Florenzano, F., Burello, L., Gelfo, F., & Petrosini, L. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0833-6 · Cited by 30
“…biology studies, large spines abundantly express AMPA receptors and are associated with large postsynaptic density, producing consequently large AMPA receptor-mediated currents (Matsuzaki et al. 2001, 2004; Kasai et al. 2003; Holtmaat et al. 2005; Noguchi et al. 2005; Bourne and Harris 2007).”
BackgroundA chemist and biologist talk to each other about caged neurotransmitters
Ellis‐Davies, G. C. R. (2013) · Beilstein Journal of Organic Chemistry · doi:10.3762/bjoc.9.8 · Cited by 30
Self-citationPopov, V. I., & Stewart, M. G. (2009) · Synapse · doi:10.1002/syn.20613 · Cited by 30
Barucker, C., Bittner, H. J., Chang, P. K. ‐., Cameron, S., Hancock, M. A., Liebsch, F., Hossain, S., Harmeier, A., Shaw, H. S., Charron, F. M., et al. (2015) · Scientific Reports · doi:10.1038/srep15410 · Cited by 32
Kitahara, Y., Ohta, K., Hasuo, H., Shuto, T., Kuroiwa, M., Sotogaku, N., Togo, A., Nakamura, K., & Nishi, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147307 · Cited by 31
“It has been proposed that synaptic responses to glutamatergic stimulation, which are determined as excitatory postsynaptic currents (EPSCs), are positively correlated with the spine volumes [15], although conflicting findings on the correlation of synaptic function with structure have been reported [16, 17].”
BackgroundShining Light on Neurons - Elucidation of Neuronal Functions by Photostimulation
Eder, M., Zieglgänsberger, W., & Dodt, H. (2004) · Reviews in the Neurosciences · doi:10.1515/revneuro.2004.15.3.167 · Cited by 31
Transfer of Neuroplasticity from Nucleus Accumbens Core to Shell Is Required for Cocaine Reward
Marie, N., Canestrelli, C., & Noble, F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030241 · Cited by 29
“Previous studies have demonstrated a positive correlation between spine size and AMPA current [55].”
BackgroundInhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo
Yang, F., You, H., Mizui, T., Ishikawa, Y., Takao, K., Miyakawa, T., Li, X., Bai, T., Xia, K., Zhang, L., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02595-5 · Cited by 38
Trafficking in neurons: Searching for new targets for Alzheimer's disease future therapies
Musardo, S., Saraceno, C., Pelucchi, S., & Marcello, E. E. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.07.019 · Cited by 29
Modeling the Shape of Synaptic Spines by Their Actin Dynamics
Bonilla-Quintana, M., Wörgötter, F., Tetzlaff, C., & Fauth, M. J. (2020) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2020.00009 · Cited by 25
“been mostly studied using the volume of the spine head ( [3–6], more details in [7]) 7 providing evidence for a link between spine-morphological and synaptic-functional 8 properties.”
MethodParajuli, L. K., Wako, K., Maruo, S., Kakuta, S., Taguchi, T., Ikuno, M., Yamakado, H., Takahashi, R., & Koike, M. (2020) · eNeuro · doi:10.1523/eneuro.0072-20.2020 · Cited by 29
“The linear relationship between spine head volume and PSD area is maintained in A53T-BAC-SNCAmice It has been well-established that spine head volume is positively correlated with both PSD area and AMPA receptor content (Wilson et al., 1983; Matsuzaki et al., 2001).”
BackgroundGeometry and the Organizational Principle of Spine Synapses along a Dendrite
Parajuli, L. K., Urakubo, H., Takahashi-Nakazato, A., Ogelman, R., Iwasaki, H., Koike, M., Kwon, H., Ishii, S., Oh, W. C., Fukazawa, Y., et al. (2020) · eNeuro · doi:10.1523/eneuro.0248-20.2020 · Cited by 27
“The magnitude of EPSPs at the soma, generated by the activation of a dendritic spine, is critically influenced by the dimensions of the spine head volume and the neck length (Matsuzaki et al., 2001; Araya et al., 2006b, 2014).”
BackgroundSpinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy?
Kopach, O., & Voitenko, N. V. (2021) · Channels · doi:10.1080/19336950.2021.1885836 · Cited by 32
“For instance, an individual “mature” (mushroomshaped) spine of a CA1 pyramidal neuron can host up to 150 AMPAR [66].”
BackgroundWnt-Frizzled Signaling Regulates Activity-Mediated Synapse Formation
Teo, S., & Salinas, P. C. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.683035 · Cited by 29
“The growth of dendritic spines is closely followed by an increase in the level of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) at dendritic spines (Matsuzaki et al., 2001; Huganir and Nicoll, 2013).”
BackgroundRecent advances in optical manipulation of cells and molecules for biological science
Kishimoto, T., Masui, K., Minoshima, W., & Hosokawa, C. (2022) · Journal of Photochemistry and Photobiology C Photochemistry Reviews · doi:10.1016/j.jphotochemrev.2022.100554 · Cited by 32
Li, B., Sumera, A., Booker, S. A., & McCullagh, E. A. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00062 · Cited by 32
Siemsen, B. M., Denton, A. R., Parrilla-Carrero, J., Hooker, K. N., Carpenter, E. A., Prescot, M. E., Brock, A. G., Westphal, A. M., Leath, M. N., McFaddin, J. A., et al. (2023) · Cells · doi:10.3390/cells12141812 · Cited by 29
Tandem triad systems based on FRET for two-photon induced release of glutamate
Picard, S., Cueto-Diaz, E. J., Génin, E., et al. (2013) · Chemical Communications · doi:10.1039/c3cc45812a · Cited by 29
Stabilizing dendritic structure as a novel therapeutic approach for epilepsy
Wong, M. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.6.907 · Cited by 29
García-López, P., García‐Marín, V., & Freire, M. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3543-06.2006 · Cited by 32
“However, the strength of these synapses might be less powerful than those with big heads because the volume of the spine head is directly proportional to the size of the postsynaptic density (Freire, 1978), the size of the presynaptic terminal (Špaèek and Hartmann, 1983; Peters, 1987), the number of AMPA postsynaptic…”
BackgroundTada, H., Koide, M., Ara, W., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131359 · Cited by 29
“Previous reports show that an influx of Ca through the CP-AMPARs is required for spine enlargement after LTP [22], and that spine enlargement may enhance its capacity to recruit AMPARs [23].”
BackgroundPhysiological roles of spine motility: development, plasticity and disorders
McKinney, R. A. (2005) · Biochemical Society Transactions · doi:10.1042/bst20051299 · Cited by 29
Boucher, J., Kröger, H., & Attila Gabor, S. I. K. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0273-x · Cited by 30
“Consistent with previous experimental data (Nusser et al. 1998; Takumi et al. 1999; Andrasfalvy and Magee 2001; Matsuzaki et al. 2001) our simulation shows that the increase of the postsynaptic response linearly increases with the number of available receptors, thus larger synapses generate larger…”
ResultNano functional neural interfaces
Wang, Y., Zhu, H., Yang, H., Argall, A. D., Luan, L., Xie, C., & Guo, L. (2018) · Nano Research · doi:10.1007/s12274-018-2127-4 · Cited by 30
Plasticity of postsynaptic nanostructure
Droogers, W. J., & MacGillavry, H. D. (2023) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2023.103819 · Cited by 28
“Similarly, spine head area correlates with PSD area and AMPA receptor-mediated responses (Holler et al., 2021; Matsuzaki et al., 2001).”
BackgroundLetrozole Potentiates Mitochondrial and Dendritic Spine Impairments Induced byβAmyloid
Chang, P. K. ‐., Boridy, S., McKinney, R. A., & Maysinger, D. (2013) · Journal of Aging Research · doi:10.1155/2013/538979 · Cited by 31
“Given the observed decrease in spine density, we subsequently investigated whether the significant decrease in spine density was subtype dependent (thin, stubby, and mushroom), which could serve as a correlate of the number of glutamatergic α-amino-3-hydroxy-5-methyl4-isoxazolepropionic (AMPA)-type receptors and synap…”
BackgroundCombining Membrane Potential Imaging with l-Glutamate or GABA Photorelease
Vogt, K. E., Gerharz, S., Graham, J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024911 · Cited by 28
“[4,20,22] or by two photon uncaging [7,36–38].”
Inaba, H., Kishimoto, T. E., Oishi, S., Nagata, K., Hasegawa, S., Watanabe, T., & Kida, S. (2016) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2016.1224639 · Cited by 28
“[83] Matsuzaki M, Ellis-Davies GC, Nemoto T, et al.”
Distance-dependent gradient in NMDAR-driven spine calcium signals along tapering dendrites
Walker, A., Neves, G., Grillo, F. W., Jackson, R. E., Rigby, M., O’Donnell, C., Lowe, A., Vizcay‐Barrena, G., Fleck, R. A., & Burrone, J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607462114 · Cited by 25
“Previous findings have established a strong correlation between spine volume and both PSD size, as well as AMPA receptors number (18, 19), but the link with NMDARs is less clear.”
BackgroundMatsui, C., Inoue, E., Kakita, A., Arita, K., Deguchi‐Tawarada, M., Togawa, A., Yamada, A., Takai, Y., & Takahashi, H. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2012.00587.x · Cited by 27
“The morphology of dendritic spines is known to correlate with the strength of their synaptic activity (10).”
BackgroundSpecificity and randomness: structure–function relationships in neural circuits
Lee, W.-C. A., & Reid, R. C. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.07.004 · Cited by 29
Tandem Systems for Two‐Photon Uncaging of Bioactive Molecules
Klausen, M., Dubois, V., Verlhac, J., et al. (2019) · ChemPlusChem · doi:10.1002/cplu.201900139 · Cited by 27
Intracellular calcium stores mediate metaplasticity at hippocampal dendritic spines
Mahajan, G., & Nadkarni, S. (2019) · The Journal of Physiology · doi:10.1113/jp277726 · Cited by 25
“Our investigation is motivated by the observation that mature spines that have ER are associated with stronger synapses and have most likely been potentiated (Matsuzaki et al. 2001; Holbro et al. 2009; Sun et al. 2014; Chirillo et al. 2015).”
BackgroundLeem, Y., Yoon, S. S., & Jo, S. A. (2020) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2019.152 · Cited by 28
“Spine morphology also contributes to synaptic plasticity and function; thin and elongated spines are motile, transient, and form weaker synapse, whereas stubby or mushroom type spines form more stable and stronger synapse with larger postsynaptic densities (PSDs) that contain larger numbers of α-amino3-hydroxy-5-methy…”
BackgroundImaging dendritic spines: molecular organization and signaling for plasticity
Suratkal, S. S., Yen, Y., & Nishiyama, J. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.08.006 · Cited by 30
Controlling cellular systems with Bhc-caged compounds
Furuta, T., & Noguchi, K. (2004) · TrAC Trends in Analytical Chemistry · doi:10.1016/s0165-9936(04)00734-4 · Cited by 27
Sexual dimorphism in estrogen-induced synaptogenesis in the adult hippocampus
Brandt, N., Vierk, R., & Rune, G. M. (2013) · The International Journal of Developmental Biology · doi:10.1387/ijdb.120217gr · Cited by 28
Regulation of synaptic structure and function by palmitoylated AMPA receptor binding protein
Misra, C., Restituito, S., Ferreira, J. M., Rameau, G. A., Fu, J., & Ziff, E. B. (2010) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2010.01.001 · Cited by 28
“The link between spine size and AMPA receptor content (Matsuzaki et al., 2001) is also in accord with our findings of elevated surface AMPA receptors in pABP-L Misra et al.”
The Role of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Treatment of Stroke
Zhao, L. R., Piao, C. J., Murikinati, S. R., & Gonzalez-Toledo, M. E. (2013) · Recent Patents on CNS Drug Discovery · doi:10.2174/1574889811308010002 · Cited by 27
In Vivo Volume Dynamics of Dendritic Spines in the Neocortex of Wild-Type and Fmr1 KO Mice
Ishii, K., Nagaoka, A., Kishida, Y., Okazaki, H., Yagishita, S., Ucar, H., Takahashi, N. K., Saito, N., & Kasai, H. (2018) · eNeuro · doi:10.1523/eneuro.0282-18.2018 · Cited by 26
“…and elimination underlie the formation and maintenance of neuronal networks, and their head sizes strongly correlate with synaptic efficacy (Matsuzaki et al., 2001, 2004; Noguchi et al., 2005; Béïque et al., 2006; Bhatt et al., 2009; Holtmaat and Svoboda, 2009; Kasai et al., 2010; Herring…”
BackgroundSelf-citationMolecular Engineering of Photoremovable Protecting Groups for Two‐Photon Uncaging
Gug, S., Bolze, F., Specht, A., et al. (2008) · Angewandte Chemie · doi:10.1002/ange.200803964 · Cited by 27
Synthesis of carbamate-type caged derivatives of a novel glutamate transporter blocker
Takaoka, K., Tatsu, Y., Yumoto, N., Nakajima, T., & Shimamoto, K. (2004) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2004.04.011 · Cited by 27
Psychostimulant-Induced Adaptations in Nucleus Accumbens Glutamatergic TransmissionPreprint
Wright, W. J., & Dong, Y. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a039255 · Cited by 29
“Newly generated synapses in the adult brain are thought to be thin or filopodia-like, consistent with nascent silent synapses during development (Maletic-Savatic et al. 1999; Matsuzaki et al. 2001; Holtmaat et al. 2006; Knott et al. 2006; Fu et al. 2012).”
BackgroundCooperative stochastic binding and unbinding explain synaptic size dynamics and statistics
Shomar, A., Geyrhofer, L., Ziv, N. E., & Brenner, N. (2017) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005668 · Cited by 25
Breach, M. R., Moench, K. M., & Wellman, C. L. (2019) · Developmental Neurobiology · doi:10.1002/dneu.22723 · Cited by 27
“For instance, AMPA receptors are more abundant in mushroom spines (Matsuzaki et al., 2001), and spine head size correlates with synaptic strength and stability (Chen, Lu, & Zuo, 2014).”
BackgroundRegan, P. L., Mitchell, S. J., Kim, S. C., Lee, Y., Yi, J. H., Barbati, S. A., Shaw, C. E., & Cho, K. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.3129-20.2021 · Cited by 29
“Since dendritic spine number and structure is tightly associated with excitatory synapse function (Kasai et al., 2010; Hayashi-Takagi et al., 2015) and correlates with synaptic AMPAR content (Matsuzaki et al., 2001), we investigated whether pTau also induces structural weakening of synapses.”
BackgroundPresynaptic supervision of cortical spine dynamics in motor learning
Sohn, J., Mototaka Suzuki, A., Youssef, M., Hatada, S., Larkum, M. E., Kawaguchi, Y., & Kubota, Y. (2022) · Science Advances · doi:10.1126/sciadv.abm0531 · Cited by 29
“Since spine size and synaptic strength are correlated (48, 49), this suggests that new spines may need to further enlarge their size for stabilization of the acquired skill.”
BackgroundDendritic spines and linear networks
Yuste, R., & Urban, R. (2004) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2005.09.014 · Cited by 26
Takusan: A Large Gene Family that Regulates Synaptic Activity
Tu, S., Shin, Y., Zago, W. M., States, B. A., Eroshkin, A. M., Lipton, S. A., Tong, G., & Nakanishi, N. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.021 · Cited by 29
“It has been established that the abundance of AMPA receptors correlates with the size of the synapse and dimensions of the dendritic spine head (Matsuzaki et al., 2001; Nusser, 2000; Takumi et al., 1999) and overexpression of GluR2 in hippocampal neurons increases spine size and density (Passafaro et al.”
Stefen, H., Chaichim, C., Power, J., & Fath, T. (2016) · Neural Plasticity · doi:10.1155/2016/2371970 · Cited by 30
“the postsynaptic membrane [20].”
Changes of Synaptic Structures Associated with Learning, Memory and Diseases
Yang, Y., Lu, J., & Zuo, Y. (2018) · Brain Science Advances · doi:10.26599/bsa.2018.2018.9050012 · Cited by 28
“Because the size of a synapse positively correlates with its strength [12, 67], these results suggest that in the aging brain, synapses are weaker and less stable, which may be related to aging-related cognitive impairments.”
EphrinB2 regulates VEGFR2 during dendritogenesis and hippocampal circuitry development
Harde, E., Nicholson, L., Cuadrado, B. F., Bissen, D., Wigge, S., Urban, S., Segarra, M., de Almodóvar, C. R., & Acker‐Palmer, A. (2019) · eLife · doi:10.7554/elife.49819 · Cited by 27
“Such an early dynamic period is essential for proper wiring, synapse formation and the establishment of neural circuits (Wong and Wong, 2000; Matsuzaki et al., 2001; Koleske, 2013) During this time, dendrite stabilization and synapse formation are strongly coupled.”
Background
Metadata
- Authors
- Matsuzaki, M., Ellis-Davies, G. C. R., Nemoto, T., Miyashita, Y., Iino, M., & Kasai, H.
- Affiliations
- National Institute for Physiological Sciences (JP)
- The University of Tokyo (JP)
- Corresponding author
- Kasai, Haruo
- Venue
- Nature Neuroscience
- Published
- 2001-10-22
- Volume
- 4
- Issue
- 11
- Pages
- 1086-1092
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4229049
- OpenAlex
- W1798313689
- Semantic Scholar
- 0791a25208e00590f1e05aade330dddd88a94dc4
- Cited by
- 1,563
- References
- 53
- Citations by year
- 2026: 30 · 2025: 49 · 2024: 45 · 2023: 70 · 2022: 64 · 2021: 90 · 2020: 71 · 2019: 76 · 2018: 75 · 2017: 65 · 2016: 78 · 2015: 84 · 2014: 75 · 2013: 75 · 2012: 81
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM 53395, R01 GM053395)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dendritic spines, AMPA receptors, spine geometry, mushroom spines, filopodia, silent synapses, CA1 pyramidal neurons, hippocampus, glutamate uncaging, excitatory synapses, synaptic plasticity
- MeSH terms
- Animals, Cells, Cultured, Dendrites, Electrophysiology, Glutamates, Hippocampus, Indoles, Mathematics, Microscopy, Fluorescence, Photolysis, Molecular Structure, Rats, Wistar, Pyramidal Cells, Receptors, AMPA, Patch-Clamp Techniques, Glutamic Acid, Excitatory Postsynaptic Potentials, Cell Surface Extensions, Rats, In Vitro Techniques
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